Outcome of patients (PTS) with advanced epithelioid hemangioendothelioma (EHE) after failure on sirolimus (S).
Authors: Claudia Giani, Rosalba Miceli, Giacomo Giulio Baldi, Antonella Brunello, Bruno Vincenzi, Carlo Morosi, Francesca Gabriella Greco, Alessandro Gronchi, Matilde Ingrosso, Anna Maria Frezza, Paolo Giovanni Casali, Silva Ljevar, Silvia Stacchiotti
Journal: Journal of Clinical Oncology (2023)

11574 Background: EHE is an ultra-rare sarcoma, showing a highly variable clinical behavior, from indolent to very aggressive. Systemic agents available for treatment of sarcoma have marginal activity in EHE. S showed antitumor effect in PDX models and pts affected by advanced EHE. However, clinical data on S in EHE are only retrospective and uncontrolled. This makes it difficult to interpret if the median progression-free survival (m-PFS) of 13 mos and the m-overall survival (m-OS) of 18.8 mos observed in the 38 progressive pts included in the largest series available (Stacchiotti et al, doi:10.1002/cncr.33247) were attributable to the antitumor effect of S or to EHE natural history. To fill this gap, we reviewed the outcome of pts included in this series who went off S. Methods: Clinical data of all EHE pts included in the above-mentioned retrospective study and treated with S for advanced disease between 2010 and 2019 were reviewed, focusing on pts who discontinued S for any reason. Progression was retrospectively categorized by RECIST 1.1 progressive disease (PD) and as “clinical progression” (CP), CP being defined as worsening of systemic symptoms and/or serosal effusion without criteria for RECIST PD. Survival analyses were performed by Kaplan-Meier method. OS was defined as the time from S start until death or last follow-up (FU), post-discontinuation OS (pOS) as the time from S discontinuation until death or last FU, post-discontinuation PFS (pPFS) as the time from S discontinuation until first evidence of progression (PD or CP) or death, post-re-challenge PFS (pR-PFS) as the time from S re-challenge until first evidence of progression (PD or CP) or death. Results: Of the 38 pts, 24 stopped S and were included in this analysis (median age = 47 yrs; serosal effusion yes/no = 9/15; S discontinuation due to: RECIST PD = 12, CP = 3, toxicity = 7; other = 2). After S discontinuation all pts had an event (PD or CP or death), and 13/24 (54%) pts did not receive further treatments, while 11/24 (46%) started again a systemic treatment. In particular, 6/24 (25%) restarted S (all after interval progression, PD or CP) with a new stable disease in 5/6 cases. At last FU, 6/24 (25%) pts were alive, 18/24 (75%) dead. At 62.2-mo m-FU (IQR 46-124), m-OS was 14.3 mos (95% CI, 7.3-21.2). Overall m-pPFS was 3.02 mos (95% CI, 1.6-4.4), m-pOS was 7.15 mos (95% CI, 4.4-9.9). m-pPFS of pts who discontinued S without evidence of progression (PD or CP) was also 3.02 mos (95% CI, 2.9-3.1). m-PFS following the re-challenge of S (m-pR-PFS) was unreached; 1 pt died following PD after 19 mos, 1 pt was alive and showed CP at 40 mos, 4 were alive and progression-free after 27, 31, 55, 94 mos. Conclusions: In our study the outcome of EHE pts who discontinued S was poor, with a m-pPFS of 3 mos and a m-pOS of 7 mos. However, pts who discontinued S for reasons other than progression benefited from S re-challenge, suggesting that in advanced EHE there is a subset of long-responders to S.